Takayoshi Naruse

Expression of Somatostatin Receptor and Effects of Somatostatin Analog on Pancreatic Endocrine Tumors

Abstract.Abstract.Purpose: Somatostatin analogs have been administered to patients with pancreatic endocrine tumors in an attempt to inhibit hormone hypersecretion and prevent tumor growth. It is speculated that their efficacy is correlated with the expression of specific subtypes of somatostatin receptors. The aim of this study was to immunohistochemically evaluate the expression of somatostatin receptor subtypes in human pancreatic endocrine tumors, and to determine whether the expression of these subtypes is correlated with the effectiveness of the somatostatin analogs.Methods: Somatostatin receptor subtypes 1, 2, and 3 (sst 1, 2, and 3) were immunohistochemically investigated in seven pancreatic endocrine tumors: four insulinomas, one VIPoma, and two nonfunctioning tumors associated with multiple endocrine neoplasia type I, using paraffin sections. Three of the four patients with insulinoma were given an octreotide injection.Results: Cells were homogeneously stained in the tumor region. More than 85% of the specimens expressed sst 1, 2, and 3. There was no difference among the immunohistochemical stainings of somatostatin receptor subtypes according to most tumor characteristics; however, the expression of sst 2 was extremely positive, and the expression of sst 3 was moderately positive in the specimen from a patient in whom the octreotide injection had proven very effective.Conclusion: These findings indicate that the efficacy of octreotide may be correlated with the density of sst 2 and 3 in an immunohistological study using paraffin sections.

The transsphincteric and transsacral approaches for the surgical excision of rectal and presacral lesions

In the decade from 1981 to 1990, 30 patients underwent a posterior transsacral approach at the Aichi Medical University Hospital for their benign or malignant rectal lesions. The operation was classified into two procedures, consisting of the transsphincteric approach and transsacral approach, in order to cope with the condition of the anal sphincter muscles; whether they were divided or not. Eleven rectal tumors were successfully excised through the opened-up rectum by using the transsphincteric approach, and excellent results were obtained without any postoperative complications. Using the transsacral approach, 2 presacral dermoid cysts and 11 rectal lesions were easily removed under direct vision. Their prognoses were excellent. The transsacral approach was also applied for the resection of recurrent rectal cancers after a radical abdominoperineal resection in 6 patients suffering from intolerable local symptoms. All the patients were free from these uncomfortable local symptoms after the surgery. The posterior transsacral operation is thus considered to be of value not only for resecting benign rectal and presacral lesions, but also for resecting malignant rectal tumors in frail subjects who are unfit for radical operation and/or recurrent rectal cancer.

Minimal thyroid carcinoma: A report of nine cases discovered by cervical lymph node metastases

From 1962 to 1983, nine patients with minimal carcinoma of the thyroid were referred to Aichi Cancer Center Hospital and to Aichi Medical University Hospital for evaluation of enlarged lymph nodes in the neck. The radiographic study and scintigraphy of the thyroid were useful in detection of small thyroid lesions. In two cases, a lymph node biopsy was required for confirmation of the diagnosis. The thyroid lesions were histologically papillary carcinoma, in all the cases. A modified neck dissection with total thyroidectomy was carried out in five patients and modified neck dissection with thyroid lobectomy was done in four cases. Nine patients were followed for 6 months to 20 years and all the patients except one are alive.

The effectiveness of administering a minimal dose of octreotide long-term prior to surgery for insulinoma: report of a case.

We report herein the case of an 80-year-old woman with insulinoma who was regarded as an unsuitable candidate for immediate surgery due to her advanced age and obesity, for whom octreotide, a long-acting analogue of somatostatin, was used to improve her hypoglycemia and hyperinsulinemia without hyperalimentation. Administering a minimal dose of octreotide for a long period resulted in the improvement of leg edema, weight control, and cardiopulmonary function, and resection of the pancreatic tumor was safely carried out without any complications.

Malignant “Triton” tumor in the thyroid —A case report—

This report presents a very rare case of a malignant “Triton” tumor developing in the thyroid. Although malignant “Triton” tumors have often been known to develop in cases of neurofibromatosis, Von Recklinghausens disease, this patient showed no clinical evidence of that disease. Total thyroidectomy including left standard radical neck dissection was followed by postoperative irradiation to the neck. Despite this, local and distant metastases developed four months after treatment and the recurrent foci did not respond to chemotherapy or irradiation. The clinical course of this case mimicked that of anaplastic carcinoma of the thyroid and interestingly, a minimal lesion of papillary adenocarcinoma was found to exist concurrently in the thyroid gland of this patient.

Serum factors attenuating the anti-tumor activity of 5-fluorouracil.

In sera of cachectic patients bearing advanced cancers, the concentration of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrotizing factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) have been reported to elevate. In this study, we investigated whether those cytokines influenced in vitro anti-tumor effect of 5-fluorouracil (5-FU) on a human colon tumor cell line, HCT-15. Pretreatment of HCT-15 cells with IL-1 beta, IL-6 or TNF-alpha did not affect the anti-tumor effect of 5-FU at various concentrations. However, IFN-gamma attenuated the anti-tumor effect of 5-FU at the concentrations of 0.1-10 IU/ml. An experiment with tritium thymidine showed that 0.1 IU/ml of IFN-gamma did not suppress the growth of HCT-15 cells. As low as 0.1 IU/ml of IFN-gamma attenuated the anti-tumor effect of 5-FU in another experimental system where HCT-15 cells were exposed to 0.1 IU/ml of IFN-gamma before and during the treatment with 5-FU. This system mimicked the clinical condition around in situ cancer cells. Treatment of HCT-15 cells with 0.1-10 IU/ml of IFN-gamma did not change their DNA histogram pattern. An immunoblotting with the antibodies to thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) in HCT-15 cells revealed that 0.1-10 IU/ml of IFN-gamma enhanced their TS and DPD expressions. Results of the immunoblotting gave some explanation to attenuation in the sensitivity of HCT-15 cells to 5-FU.

Mitogenic Activity of Gelatin to Murine Spleen Cells

We reported previously that gelatin stimulates the growth of spleen cells in vitro. Tritium thymidine (3H-TdR) uptake into phytohemagglutinin (PHA)-stimulated spleen cells as well as intact spleen cells was augmented by gelatin. These findings suggest that gelatin serves as a mitogen for lymphoid cells. In this study, the target of action of gelatin was investigated. Tritium thymidine uptake into T cell-rich fraction was enhanced by incubation with 7.5 mg/ml of gelatin for 48 hours. The level of 3H-TdR uptake into B cell-rich fraction was not definitely increased by gelatin. Flow cytometric analysis confirmed these findings. Namely, it showed that treatment of spleen cells with 7.5 mg/ml gelatin increased a ratio of CD3-positive cells and decreased that of CD19-positive cells. Tritium thymidine uptake into natural killer cell-rich fraction was augmented by gelatin in a similar fashion to T cell-rich fraction. Tritium thymidine uptake into macrophages was very low and not affected by gelatin. Tritium thymidine uptake into macrophage-precursors was very low but was enhanced by gelatin. These findings suggest that gelatin could be used as an agent of cancer biotherapy.

Clear Cell Carcinoma of the Thyroid. A Case Report

A rare case of clear cell carcinoma of the thyroid is presented herein. A 31-year-old male had a large soft tumor in the right lobe of the thyroid which showed a hot nodule on scintigram with99mTc. A right hemithyroidectomy was thus performed after the preoperative diagnosis of a functioning tumor had been made. At surgery, a tiny nodule behind the tumor was found and the histopathological diagnoses of the large tumor and the tiny nodule were clear cell carcinoma and papillary carcinoma, respectively. The thyroglobulin stain was positive in the cytoplasm of many clear cells and scattered colloid. This patient has been well without any evidence of recurrence over the past five years following surgery. The biological characteristics of clear cell carcinoma of the thyroid are discussed in this report.

Pheochromocytoma without specific symptoms

A 72-year-old Japanese woman with pheochromocytoma, who had had no characteristic symptoms was treated. A large retroperitoneal tumor was discovered incidentally by sonographic examination for mild upper abdominal pain and, with CT-scan and abdominal angiography confirmed that the tumor originated in the right adrenal gland. The tumor was suspected of being a pheochromocytoma because preoperative laboratory examinations revealed only a mild elevation of daily urinary excretions of adrenaline and noradrenaline. Provocation tests for pheochromocytoma and even angiographic examination revealed no diagnostic change in serum levels of catecholamines and distinctive clinical signs were nil. Thus, surgery was performed without preoperative prescription of any catecholamine blockade. During the surgery, the blood pressure and pulse rate fluctuated considerably. A non-functioning pheochromocytoma detected incidentally must be preoperatively managed as a functioning one, even in the absence of specific symptoms of pheochromocytoma.

Bone metabolic analysis in patients with primary hyperparathyroidism

Surgical treatment for primary hyperparathyroidism (PHPT) improves not only the calcium and phosphate metabolism but also the bone metabolism. This study was conducted to analyze the bone metabolism after PHPT operations. Bone mineral density (BMD) was measured by dual-photon absorptiometry in 50 patients before and after operation. Osteocalcin (OC) and alkaline-phosphatase activity (Alp) in serum were measured before and after surgery as markers of bone formation, and urinary deoxypiridinorine (DPD) as an index of osteoclast activity. The 50 patients under study were 40 women (80%) and ten men (20%). Increases in BMD at the lumbar spine were remarkable at three months following operation. Slow but steady progress was made until six months, reaching a plateau thereafter. The increase in BMD of lumbar spine was approximately 10%. Urinary DPD was the most sensitive among the three bone metabolic markers. Although serum Alp and OC remained high after operation, urinary DPD was normalized earlier. The discrepancy of bone formation and resorption was shown after operation and this contributed to the increases in BMD in the first six months.